The present invention relates generally to analysing and reporting patient specific medical information.
Recently, a significant advance in measurement techniques used to analyze blood plasma lipoprotein samples was achieved. Lipoproteins are the spherical particles that transport cholesterol, triglycerides, and other lipids in the bloodstream. The advanced measurement technique employs NMR spectroscopy to provide additional (higher-order) patient-specific information over the types of information typically provided under routine conventional analysis methods. See U.S. Pat. No. 4,933,844 to Otvos, entitled xe2x80x9cMeasurement of Blood Lipoprotein Constituents by Analysis of Data Acquired From an NMR Spectrometerxe2x80x9d and U.S. Pat. No. 5,343,389 to Otvos, entitled xe2x80x9cMethod and Apparatus for Measuring Classes and Subclasses of Lipoproteins.xe2x80x9d The contents of these documents are hereby incorporated by reference as if recited in full herein. Unlike conventional xe2x80x9croutinexe2x80x9d laboratory lipoprotein blood tests, the lipoprotein analysis provided by the NMR spectral analysis now more easily provides lipoprotein subclass information, which had, until this advance, been generally inaccessible to clinicians. This subclass information can provide information corresponding to the sizes of the lipoprotein particles that make up a person""s lipoprotein constituents.
Lipoprotein subclass information is not included in conventional commercially prepared lipid panels. The conventional panels typically only provided information concerning total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol (generally a calculated value), and high-density lipoprotein (HDL) cholesterol. In contrast, the NMR analysis can provide information about (a) the concentrations of six subclasses of very low density lipoprotein (VLDL), four subclasses of LDL (including intermediate-density IDL), and five subclasses of HDL, (b) average LDL particle size (which can be used to categorize individuals into LDL subclass pattern-determined risk), and (c) LDL particle concentration.
The subclass information now available with the NMR spectral analysis can be a more reliable indicator of a patient""s risk to develop coronary heart disease. Indeed, recent scientific research has shown that various subclasses of lipoproteins may provide more reliable markers of the metabolic conditions that predispose individuals to a greater or lesser risk of heart disease. However, the NMR spectral analysis can also provide higher-order information about the levels of variously atherogenic or antiatherogenic subclasses that make up each of the major lipoprotein classes.
This subclass information can provide a clear indication about a patient""s propensity to develop coronary heart disease. Unfortunately, this additional information can confuse a reviewer as to the meaning of the data, and further, the additional information can be difficult to analyze in a readily discernable manner. For example, a typical NMR lipoprotein analysis can include at least fifteen more values of lipoprotein concentration and size than is provided by standard lipoprotein panels. There is, therefore, a need to analyze and present the lipoprotein-based information in a manner or format which is visually easy to read and understand and which provides a useful coronary heart disease risk assessment.
It is therefore an object of the present invention to provide a method to analyze patient-specific NMR based lipoprotein measurements in a manner which yields a reliable indicator of an associated risk of developing coronary heart disease.
It is an additional object of the present invention to provide a lipoprotein profile analysis with subclass information with an easily read display format.
It is also an object of the present invention to provide a lipoprotein-based risk assessment which analyzes a patient""s measured major lipoprotein constituent values and/or selected subclass information and presents them in a format in which a patient""s specific values are presented in a reader-friendly format.
It is a further object of the present invention to provide a method of generating a customized report at a commercial volume and which can analyze and/or report a patient""s risk factors for coronary heart disease based on NMR-based measurements of lipoprotein constituents.
It is still another object of the invention to alert the patient or physician of a reduced lipoprotein constituent value for a secondary prevention goal for patients with underlying metabolic disorders.
It is an additional object of the present invention to provide a system for measuring lipoprotein constituents and analyzing the constituent values in a manner which determines CHD risk.
These and other objects of the present invention are provided by a method for identifying a patient with an increased risk of coronary heart disease by analyzing the patient""s NMR lipoprotein constituent measurements. This analysis includes determining a risk for a specific constituent identified as having an independently predictive factor (in isolation of the other constituent values) and for a combination of certain of the constituent measurement values. Preferably, the combination method identifies whether the patient""s results provide a positive match with two key NMR measured lipoprotein factors. The first factor is the determination of the presence of atherogenic dyslipidemia (i.e., a clustering of predetermined level moderate, borderline, or positive NMR subclass or constituent based risk values) and the second factor is the detection of an elevated number of NMR measured LDL particles. Advantageously, this type of risk analysis is typically more accurate than the plasma apo B level techniques used in the past, and can provide a more reliable indictor as it more closely corresponds to a patient""s true lipoprotein composition.
In particular, a first aspect of the present invention is directed to a method for assessing a patient""s risk of coronary heart disease based on personalized NMR measured lipoprotein-based information. The method includes generating NMR-based lipoprotein measurement values for a patient""s blood plasma or serum sample, the NMR-based lipoprotein measurement values comprising a plurality of lipoprotein constituent values including a constituent value for LDL particle concentration. The LDL particle concentration is compared with predetermined test criteria for determining whether the LDL particle concentration is elevated and a plurality of NMR-based lipoprotein constituent values are compared to predetermined test criteria to determine the presence of atherogenic dyslipidemia. A patient""s risk of coronary heart disease is assessed based on one or more of the LDL particle elevated concentration level and the presence (or absence) of atherogenic dyslipidemia.
In a preferred embodiment, the NMR-based lipoprotein constituent values include the major lipoprotein constituents of total cholesterol, LDL concentration in cholesterol equivalents, HDL concentration in cholesterol equivalents, and triglycerides, and the measured lipoprotein constituent values also include the values associated with LDL size, LDL particles, large HDL cholesterol, and large VLDL triglyceride. It is also preferred that the NMR based lipoprotein constituent values used to determine the presence of atherogenic dyslipidemia is independent to the LDL particle concentration value (i.e., does not include the isolated LDL particle concentration value as part of the subtest criteria for determining atherogenic dyslipidemia). Preferably, the predetermined test criteria for determining the presence of an elevated number of LDL particles is set at a value which is in about the upper 50% of the population (at least moderately elevated). Of course, the presence of atherogenic dyslipidemia when an elevated LDL particle concentration also exists is particularly indicative of the presence of a higher-risk metabolic condition.
Another aspect of the present invention is directed to a method of presenting NMR derived lipoprotein subclass information in a two-dimensional window. The method includes obtaining a plurality of lipoprotein constituent values associated with NMR based lipoprotein measurements including the values associated with LDL size, LDL particles, large HDL cholesterol, and large VLDL triglyceride and identifying a risk level associated with coronary heart disease for each of the obtained NMR based lipoprotein constituent values. The obtained lipoprotein constituent values are then analyzed to determine the associated risk level and the obtained lipoprotein constituent values are arranged in a display format which positions the lipoprotein constituent values adjacent to a corresponding risk analysis portion, wherein the risk analysis portion has a plurality of discrete segments characterizing the constituent value""s determined risk level. The discrete risk segment corresponding to the actual constituent value within the respective risk analysis portion is visually enhanced such that the risk associated with the lipoprotein constituent value is readily apparent. Preferably, the obtaining step also obtains the NMR based lipoprotein constituent values for the major lipoprotein constituents of total cholesterol, LDL concentration in cholesterol equivalents, HDL concentration in cholesterol equivalents, and triglycerides. It is also preferred that the risk analysis for LDL concentration in cholesterol equivalents and the LDL particle concentration includes four discrete risk segments (corresponding to optimal, desirable, borderline-high, and high risk) and wherein each of the discrete risk segments corresponds to a predetermined level associated with its occurrence in the general population. Preferably, the remainder of the lipoprotein constituent values risk analysis segments are configured with three discrete segments, and the risk analysis discrete segments for the non-major lipoprotein constituent values are configured to mirror the risk level defined for the risk analysis discrete segments for the major lipoprotein constituents. (Typically, the risk analysis segment defines the risk level such that it corresponds to the occurrence of the value as defined by a population percentile).
In a preferred embodiment, the optimal value is a reduced target value for secondary prevention.
Another aspect of the present invention is an automatically produced lipoprotein report including data corresponding to NMR-derived measurements. The report comprises a first lipid profile segment comprising a plurality of NMR derived major lipoprotein constituent values, wherein each major lipoprotein value has an associated risk analysis portion and a second subclass profile segment comprising a plurality of NMR derived subclass variables, each subclass variable having an associated risk analysis portion which is configured to visually enhance the risk of developing coronary heart disease for each of the plurality of subclass variable information. The lipoprotein report is generated at a commercial scale at automatically generated by a computer based on NMR derived patient-specific information. Further, at least the subclass profile segment includes a reduced target value associated with at least one subclass value associated with a goal of secondary prevention, thereby facilitating the awareness of the existence of an underlying metabolic disorder and providing a visual reminder to pursue a more aggressive reduction of at least one lipoprotein value compared to the general population.
In a preferred embodiment, the reduced target value is identified as an optimal risk category for both the LDL concentration in cholesterol equivalents and the LDL particle concentration in the risk analysis portions. It is also preferred that the report include a coronary heart disease risk assessment module. The risk assessment module provides additional information about coronary heart disease risks associated with an elevated number of LDL particles and the determination of the presence of atherogenic dyslipidemia associated with a clustering of selected abnormal subclass values.
Still another aspect of the invention is an automatically produced lipoprotein report which is generated at a commercial laboratory based on data corresponding to NMR-derived measurements. The automated report comprises a subclass profile segment comprising a plurality of patient-specific NMR derived lipoprotein constituent values, each constituent value having an adjacently positioned associated risk analysis portion which visually identifies the value with one of at least three discrete risk categories corresponding to a coronary heart disease risk level associated with the NMR-derived measurement value. Preferably, the automatically produced lipoprotein report includes LDL particle concentration as one of the NMR derived lipoprotein constituent values and the corresponding risk analysis portion includes four risk categories: one associated with a desirable concentration level; one associated with a borderline-high level; one associated with an increased or higher risk level; and one associated with an optimal level corresponding to a goal for secondary prevention.
An additional aspect of the present invention is a computer program product for personalized lipoprotein-based risk assessment. The computer program product comprises a computer readable storage medium having computer readable program code means embodied in the medium. The computer-readable program code means comprising a computer readable program code means for generating NMR-based lipoprotein measurement values for a patient""s blood sample, the lipoprotein measurement values including at least one subclass variable value. The computer program product also includes a computer readable program code means for comparing the at least one patient lipoprotein subclass variable value with predetermined test criteria for determining whether the at least one subclass variable value is associated with a higher or lower risk of developing coronary heart disease and computer readable program code means for identifying, for the at least one measured subclass variable value, the corresponding risk level associated with coronary heart disease. The computer program product also includes a computer readable program code means for providing a risk analysis portion adjacent to the measured lipoprotein values, the risk analysis portion displaying information corresponding to higher and lower coronary heart disease risk. The measured value is visually enhanced in the risk analysis portion to visibly indicate the level of risk associated therewith to thereby provide a contemporaneous reference guideline for interpretation of the measured value. The computer program product additionally includes a computer readable program code means for comparing a plurality of the NMR-based lipoprotein measurement values to predetermined test criteria to determine the presence of atherogenic dyslipidemia.
In a preferred embodiment, the NMR-based lipoprotein values include the major lipoprotein constituents of total cholesterol, LDL concentration in cholesterol equivalents, HDL concentration in cholesterol equivalents, and triglycerides, and the subclass values associated with LDL size, LDL particles, large HDL cholesterol, and large VLDL triglyceride, and the computer program product further comprises computer readable program code means for presenting the lipoprotein measurement values such that each of the lipoprotein measurement values is substantially aligned. It is also preferred that the risk analysis portion for each of LDL concentration in cholesterol equivalents and LDL particles is divided into four risk categories, and that the remainder of the risk analysis portions is divided into three discrete segment risk categories.
Preferably, for the reports, methods, and computer program products directed to lipoprotein information, the measured lipoprotein values include (a) the major lipoprotein constituents of total cholesterol, LDL concentration in cholesterol equivalents, HDL concentration in cholesterol equivalents, and triglycerides and (b) the LDL size and the concentration level of LDL particles, large HDL cholesterol, and large VLDL triglyceride.
The present invention is advantageous because it provides NMR-derived lipoprotein results with associated risk information in a format that is easy to understand and aesthetically pleasing. Further, the patient""s specific subclass profile is presented in the risk assessment report in a graphically enhanced or visually emphasized format so the clinician or layman can easily understand the risk category associated with one or more of a patient""s subclass values. Further, the customized report is provided in a computer program product allowing mass or commercial level automated production of a summary report which includes a risk analysis portion which can be customized to report the patient""s results in a visually enhanced format. Advantageously, the report or risk assessment method flags or alerts the treating physician or patient as to the reduced target goal for LDL concentration and LDL particle concentration for patients with underlying metabolic disorders such as established or previously diagnosed coronary heart disease, diabetes, or other vascular disorders. This secondary prevention goal is preferably visibly presented to alert and facilitate the ongoing counseling for such a patient to reinforce the importance of behavioral modifications or other therapy.